Date Published: October 5, 2011
Publisher: Hindawi Publishing Corporation
Author(s): Ghee Young Kwon, Jae Y. Ro.
Micropapillary carcinoma (MPC) of urinary tract is an uncommon variant of urothelial carcinoma with significant diagnostic and prognostic implications. Though MPC shows characteristic microscopic features, there exists interobserver variability and also it needs to be differentiated from the metastasis from other organs. The prognosis is generally poor, depending on the proportion of the micropapillary component in some reports. Early cystectomy in cases with only lamina propria invasion may be indicated according to recent studies. This review outlines the general features of this entity and briefly comments on the controversies and the recent development.
Micropapillary carcinoma (MPC) of the urinary tract is a well-recognized variant of urothelial carcinoma (UC) characterized by distinct histologic features and aggressive clinical course. Table 1 shows urothelial carcinoma and its variants including MPC. MPC is worthy of note for its implications regarding both diagnosis and clinical management. Despite increased awareness of the entity and recent development in the understanding into its pathogenesis, there still exist controversies concerning certain aspects of this rare tumor. This paper will outline the general features of this entity and briefly comment on the controversies and the recent development.
At least 500 cases of MPC of the bladder have been reported as a special variant since its first description in 1994 by Amin et al. , and MPC is reported to comprise 0.6 to 8.2% of urothelial carcinoma, with later series reporting the higher end of the spectrum [2, 3]. The recent rise in incidence appears to reflect the increased awareness of this entity, and the variable proportion occupied by this tumor is evidently due to a lack of established criteria for diagnosis and less-than-perfect interobserver reproducibility, both of which issue will be addressed later in this paper. This tumor predominantly affects male with male to female ratio of 5 : 1 to 10 : 1 which is higher than that for conventional UC which is 3 : 1 [1, 4–7].
Gross morphology of MPC is variable, and there are no unique features to distinguish it from conventional UC or other variants. MPC can present as papillary, sessile, polypoid, ulcerative, or infiltrative mass, and the size can also be variable from microscopic focus to over 10 cm .
The defining microscopic feature of MPC is micropapillary architecture reminiscent of the papillary configuration seen in ovarian papillary serous tumors. The micropapillary pattern of MPC can present either (i) on the mucosal surface as slender delicate processes which are usually devoid of a fibrovascular core and appear as glomeruloid bodies on cross section (Figure 1), or (ii) in the invasive component as small tight cell nests or balls contained in lacunae or stromal retraction spaces (Figure 2), mimicking lymphovascular invasion (LVI). The nuclei of tumor cells are frequently of high grade, showing reversed polarity to the external surface of tumor nests (Figure 3). A small proportion of the tumor-containing spaces represents actual lymphovascular invasion as evidenced by immunostaining for endothelial markers such as factor VIIIR-Ag, Ulex europaeus agglutinin I lectin, CD 31, CD34, and D2-40 (Figure 4). Although LVI is present in most cases of invasive MPC if adequately sampled and diligently searched for, a vast majority of the tumor-containing lacunae lack endothelial lining and do not constitute true LVI. Psammoma bodies, found in ovarian papillary serous neoplasia, are vanishingly rare in urinary tract MPC. The overwhelming majority of this tumor shows deep muscle invasion (Figure 5), and thus, it is recommended to alert clinicians regarding the invasive potential of this tumor when the biopsy is obtained mainly from the superficial layer and proper muscle is not included in the biopsy [1, 8].
The most important differential diagnosis for urinary tract MPC is its distinction from conventional UC with prominent retraction artifacts, which issue has been elegantly addressed in a recent consensus study by Sangoi et al. . In that study, the agreement among uropathologists for the diagnosis of MPC was only moderate and the authors provide a few diagnostically useful morphologic observations. In their opinion, which is shared by us, multiple or small tumor nests in lacunar spaces are important diagnostic clues, while large or branching nests with anastomoses and confluence argue against the diagnosis of MPC. In this context, it appears that a sizable proportion of disagreement is from cases which display an intimate mixture of tumor nests displaying variable-sized tumor nests in diverse configuration. We suggest that it would be reasonable to diagnose MPC only when there is at least one high-power-field area of pure classic MPC without readily identifiable contradicting features. There are no immunohistochemical markers to reliably differentiate MPC from conventional UC. Though it has been reported that MUC1, CA125, Her/neu, and KL-6 might be specific for MPC , these results were not supported by other studies .
There is a paucity of data regarding the pathogenesis of MPC. However, one interesting aspect is the reversed polarity of tumor cells. With that, tumor cells facing the stroma acquire apical secretory properties evidenced by ultrastructural examination and immunostaining for MUC1, a surface glycoprotein present on the apical/luminal surface. This unusual interface might lead to the detachment of tumor cells from the stroma, facilitating stromal invasion .
Both clinical and pathological implication has undoubtedly contributed to the establishment of MPC as a distinct entity along with its wide recognition. Clinically, this tumor is almost invariably muscle invasive at the time of presentation with frequent metastasis to lymph nodes and distant organs. Thus, it is imperative to get a deep biopsy when the proper muscle invasion is not found on superficial sampling.